Chan, Chun Kit. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 147-161). / Abstracts in English and Chinese. / Chapter Chaper 1 --- Introduction --- p.1 / Chapter 1.1 --- General introduction to cerebral stroke --- p.1 / Chapter 1.2 --- Different types of cerebral stroke --- p.2 / Chapter 1.3 --- Statistics --- p.3 / Chapter 1.4 --- Symptoms of cerebral stroke --- p.4 / Chapter 1.5 --- Complications of cerebral stroke --- p.5 / Chapter 1.6 --- Risks and preventions of cerebral stroke --- p.6 / Chapter 1.7 --- Cerebral stroke treatment --- p.8 / Chapter 1.8 --- Post stroke rehabilitation --- p.11 / Chapter 1.9 --- Mechanisms of stroke --- p.15 / Chapter 1.9.1 --- Energy production failure and loss of ionic homeostasis --- p.15 / Chapter 1.9.2 --- Excitotoxicity --- p.16 / Chapter 1.9.3 --- Calcium ions mediated toxicity --- p.17 / Chapter 1.9.4 --- Passive neuronal cell death --- p.18 / Chapter 1.9.5 --- Oxidative stress --- p.19 / Chapter 1.9.6 --- Inflammation --- p.22 / Chapter 1.9.7 --- Apoptosis --- p.25 / Chapter 1.10 --- Potential therapeutic agents for cerebral stroke --- p.24 / Chapter 1.10.1 --- Anti-oxidative enzyme and free radical scavengers --- p.24 / Chapter 1.10.2 --- Ions channel blockers and glutamate antagonists --- p.26 / Chapter 1.10.3 --- Anti-inflammatory agent --- p.28 / Chapter 1.10.4 --- Anti-apoptotic agent --- p.28 / Chapter 1.11 --- Experimental model of cerebral ischemia-reperfusion --- p.29 / Chapter 1.11.1 --- In vitro model (oxygen and glucose deprivation model) --- p.29 / Chapter 1.11.2 --- In vivo model (Middle cerebral artery occlusion) --- p.31 / Chapter 1.12 --- Traditional Chinese Medicine (TCM) --- p.32 / Chapter 1.12.1 --- General Introduction to Traditional Chinese Medicine --- p.32 / Chapter 1.12.2 --- TCM and cerebral stroke --- p.33 / Chapter 1.12.3 --- Chinese compound formula --- p.34 / Chapter 1.12.4 --- Introduction to individual herb --- p.34 / Chapter 1.12.4.1 --- Astragali Radix (Pinyin name: Huangqi) --- p.34 / Chapter 1.12.4.2 --- Rhizoma Chuanxiong (Pinyin name: Chuanxiong) --- p.35 / Chapter 1.12.4.3 --- Radix Salviae Miltorrhizae (Pinyin name: Danshen) --- p.35 / Chapter 1.12.4.4 --- Cassia Obtusifolia Linne (Pinyin name: Jue Ming Zi) --- p.36 / Chapter 1.12.4.5 --- Radix Glycyrrhizae (Pinyin name: Gancao) --- p.37 / Chapter 1.12.4.6 --- Radix Angelicae Sinensis (Pinyin name: Dongquai) --- p.37 / Chapter 1.12.4.7 --- Paeoniae Veitchii Radix (Pinyin name: Chi Shao) --- p.38 / Chapter 1.12.5 --- Salvianolic acid B --- p.39 / Chapter 1.13 --- Aim of study --- p.40 / Chapter Chapter 2 --- Materials and Methods --- p.41 / Chapter 2.1 --- Materials --- p.41 / Chapter 2.1.1 --- Drug --- p.41 / Chapter 2.1.1.1 --- Herbal Medicine --- p.41 / Chapter 2.1.1.2 --- Herbal extraction of PSR --- p.42 / Chapter 2.1.1.3 --- Herbal extraction of individual herb --- p.43 / Chapter 2.1.1.4 --- Salvianolic acid B --- p.43 / Chapter 2.1.2 --- Chemical --- p.44 / Chapter 2.1.3 --- Animal --- p.48 / Chapter 2.2 --- Methods --- p.49 / Chapter 2.2.1 --- (AAPH)- induced erythrocyte hemolysis --- p.49 / Chapter 2.2.2 --- Cell Culture study --- p.51 / Chapter 2.2.2.1 --- Cell Line --- p.51 / Chapter 2.2.2.2 --- Cell differentiation --- p.52 / Chapter 2.2.2.3 --- In vitro model of ischemia - Oxygen glucose deprivation (OGD) experiment --- p.53 / Chapter 2.2.2.4 --- Cell viability assay --- p.54 / Chapter 2.2.3 --- In vivo Study --- p.54 / Chapter 2.2.3.1 --- Cerebral blood flow (CBF) measurement --- p.54 / Chapter 2.2.3.2 --- In vivo transient focal cerebral ischemia model - Middle cerebral artery occlusion (MCAo) --- p.55 / Chapter 2.2.3.3 --- Administration of PSR --- p.57 / Chapter 2.2.3.4 --- Administration of salvianolic acid B (SAB) --- p.59 / Chapter 2.2.3.5 --- Measurement of brain infarct volume --- p.60 / Chapter 2.2.3.6 --- In vivo anti-oxidative enzyme activity determination in the brain --- p.61 / Chapter 2.2.3.6.1 --- Brain tissue preparation --- p.61 / Chapter 2.2.3.6.2 --- Tissue homogenization and protein extraction --- p.61 / Chapter 2.2.3.6.3 --- Protein concentration determination --- p.63 / Chapter 2.2.3.6.4 --- Catalase activity determination in the brain --- p.63 / Chapter 2.2.3.6.5 --- Glutathione Peroxidase (GPx) activity determination in the brain --- p.64 / Chapter 2.2.3.6.6 --- The Superoxide Dismutase (SOD) activity determination in the brain --- p.65 / Chapter 2.2.3.7 --- Behavioral Evaluation --- p.66 / Chapter 2.2.3.7.1 --- Neurological behavioural test --- p.66 / Chapter 2.2.3.7.2 --- Shuttle box escape experiment --- p.67 / Chapter 2.3 --- Statistical analyses --- p.71 / Chapter Chapter 3 --- Results --- p.72 / Chapter 3.1 --- In vitro model of ischemia - Oxygen glucose and deprivation (OGD) experiment --- p.72 / Chapter 3.2 --- AAPH assay of PSR --- p.75 / Chapter 3.3 --- AAPH assay of individual herb --- p.77 / Chapter 3.4 --- Brain slices after middle cerebral artery occlusion (MCAo) experiment --- p.81 / Chapter 3.5 --- Brain infarct volume of single dose protocol --- p.83 / Chapter 3.6 --- Neurological behavioural test of single dose protocol --- p.85 / Chapter 3.7 --- Brain infarct volume of double doses protocol --- p.87 / Chapter 3.8 --- Neurological behavioural test of double doses protocol --- p.89 / Chapter 3.9 --- Determination of superoxide dismutase (SOD) activity in the brain --- p.91 / Chapter 3.10 --- Determination of glutathione peroxidase (GPx) activity in the brain --- p.93 / Chapter 3.11 --- Determination of catalase activity in the brain --- p.95 / Chapter 3.12 --- Brain infarction volume of Salvianolic acid B (SAB) treatment --- p.98 / Chapter 3.13 --- Neurological behavioural test of SAB treatment --- p.100 / Chapter 3.14 --- Shuttle box performance in training and testing series --- p.102 / Chapter 3.15 --- Change in shuttle box performance (% avoidance c.f. last day of training) in testing series --- p.104 / Chapter 3.16 --- Escape latency in testing and training series --- p.107 / Chapter 3.17 --- Change in escape latency (c.f. last day of training) in testing series --- p.109 / Chapter 3.18 --- Brain infarct volume of shuttle box escape experiment --- p.112 / Chapter 3.19 --- Neurological score in shuttle box escape experiment --- p.114 / Chapter Chapter 4 --- Discussion --- p.117 / Chapter 4.1 --- The protective effect of PSR in in vitro oxygen and glucose deprivation (OGD) on human neuroblastoma SH-SY5Y cell line --- p.117 / Chapter 4.1.1 --- OGD model and cell line --- p.117 / Chapter 4.1.2 --- Protective effect of PSR in OGD experiment --- p.118 / Chapter 4.1.3 --- Free radical scavenging property of PSR --- p.120 / Chapter 4.2 --- The protective effects of PSR in in vivo middle cerebral artery (MCAo) model --- p.121 / Chapter 4.2.1 --- The shortcomings of in vitro OGD model --- p.121 / Chapter 4.2.2 --- Development of in vivo MCAo model and TTC staining --- p.122 / Chapter 4.2.3 --- Protective effect of PSR in MCAo experiment (single dose protocol) --- p.124 / Chapter 4.2.4 --- Protective effect of PSR in MCAo experiment (double doses protocol) --- p.125 / Chapter 4.2.5 --- The effect of PSR toward neurological deficits --- p.127 / Chapter 4.2.6 --- Anti-oxidative effects of PSR in MCAo model --- p.128 / Chapter 4.3 --- The protective effects of SAB in in vivo middle cerebral artery (MCAo) model --- p.130 / Chapter 4.3.1 --- Free radical scavenging property of different herbs --- p.130 / Chapter 4.3.2 --- Selection of pure compound that used to treat stroke --- p.131 / Chapter 4.3.3 --- Protective effect of Salvianolic B in MCAo experiment --- p.132 / Chapter 4.3.4 --- The effect of SAB toward neurological deficits --- p.133 / Chapter 4.4 --- The effects of PSR and SAB on stroked rats' performance in shuttle box escape experiment --- p.134 / Chapter 4.4.1 --- Establishment of shuttle box escape experiment --- p.134 / Chapter 4.4.2 --- Effects of PSR and SAB on avoidance performance --- p.135 / Chapter 4.4.3 --- Effects of PSR and SAB on escape latency --- p.138 / Chapter 4.5 --- Assessment on the contribution of SAB to the protective effect of PSR --- p.140 / Chapter 4.6 --- Comparison of acute and chronic testing --- p.140 / Chapter 4.6.1 --- The protective effect of the drugs (Histopathological examination) --- p.140 / Chapter 4.6.2 --- The severity of motor deficit (Neurological score) --- p.141 / Chapter Chapter 5 --- Conclusion and Future prospect --- p.143 / Chapter 5.1 --- Conclusion --- p.143 / Chapter 5.2 --- Future prospect --- p.144 / References --- p.147

Psychotropic drugs are mind affecting compounds. They range in type from illegal narcotic analgesics such as heroin, to prescribed major tranquillisers used for treatment of psychotic states, to prescribed minor tranquillisers such as the benzodiazepines, Valium and Mogadon, to the freely available, over the counter drugs, Aspirin and Panadol. Overseas and Australian data show the minor tranquilliser group, benzodiazepines, first introduced on the pharmaceutical scene in the early 1960s, to be the most commonly prescribed psychotropic drugs. Their popularity with medical practitioners as prescription drugs for conditions of anxiety, stress, insomnia and some forms of epilepsy, arises from the advertised inference by drug companies that they are free from any side effects in the patient such as dependence, tolerance and on termination of treatment, absence of withdrawal syndrome. Benzodiazepines were first introduced as a substitute for the well known dependence producing barbiturate based sedatives. Overseas and Australian data show women are prescribed psychotropic drugs, particularly benzodiazepines, twice as often as men and in many instances for conditions unrelated to those for which the drugs are recommended. Australian data comes from two sources, official statistics such as the Pharmaceutical Benefits Scheme and from surveys of drug use. Both sources of data are incomplete, inaccurate and in many cases misleading. The true picture of prescribed psychotropic drug use in Australia therefore lacks resolution and in all probability underestimates prevalence and patterns of use in the community. There is no data on the prevalence and patterns of use of prescribed psychotropic drugs in the Australian Capital Territory. It was therefore deemed appropriate to conduct a survey to determine their prevalence and patterns of use. The survey was confined to women for several reasons: Women are a target group in the Commonwealth and State Government 'Drug Offensive'; evidence from studies overseas and in Australia shows that women are prescribed psychotropic drugs, particularly benzodiazepines, twice as often as men; Australian data suggests that this trend is uniform and therefore the Australian Capital Territory should be no different. Data shows that doctors, particularly General Practitioners, are the main source of prescribed psychotropic drugs. The main psychotropic drugs prescribed by general practitioners are benzodiazepines. It was therefore deemed appropriate to conduct a survey of general practitioner's attitudes, knowledge and beliefs about the appropriate use of benzodiazepines as these factors carry weight in a doctor's prescribing habits. The survey of women was conducted using a standardised, structured, telephone survey on a random sample of 120 women in the Australian Capital Territory. The results of the survey show that 40% of the sample had used prescribed psychotropics at some stage in their lives. Most users were older women, married, well educated and working full time. Level of knowledge about the drug was low, compliance with respect to use was high. Most prescribed psychotropic drugs were obtained from a doctor. There appears to be little drug sharing or concurrent drug use. Half of the prescribed psychotropics were benzodiazepines the other half were mostly anti-depressants. Use of over the counter psychotropics was very high. The survey of general practitioners was conducted using a standardised, structured mailed questionnaire distributed to a random sample of 25 general practitioners in the Australian Capital Territory. The results show the majority of doctors prescribe the drugs for common indications (anxiety, stress, insomnia and some forms of epilepsy) in excess of one week. For specific anxiety states however, most prescribe the drugs along with some form of counselling. The majority of doctors (77%) think counselling is not as effective as drug treatment. All doctors surveyed think patients should be advised of the drugs effects on driving and machinery operation; the drugs should not be shared with others; that the drugs should not be terminated abruptly; the drugs should not be used concurrently with alcohol. The majority (92%) believe benzodiazepines are over prescribed and most doctors (77%) believe the drugs produce dependence in patients. The majority (58%) believe women of child bearing age are at risk using benzodiazepines while 50% think pregnant women are at risk. The majority of doctors did not believe that people older than 60 years of age are at risk but most believe children are at risk. The findings of both surveys have implications for health educators and others with a concern for drug education in the community. Recommendations arising from this study have been made. They are presented at the conclusion of this thesis.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 4 uppsatser.

 As the aging in reproductive system proceeds, females will eventually enter the period of menopause, during which a series of physiological changes occurs. The decline of estrogen level during menopausal transition is thought to associate with various menopausal symptoms. Although hormone replacement therapy can be adopted to deal with the estrogen-deficient state, side effects such as cancer risk cannot be overlooked. Alternatively, Erxian Decoction (EXD), a Chinese medicine formula for treating menopausal symptoms has been used clinically for more than 60 years without adverse effects reported. Some pharmacological properties of EXD have been reported in previous research, which are thought to be contributed by its multiple bioactive components. Thus in the present study, the pharmacological properties of EXD have been further evaluated. The drug compatibility of Traditional Chinese Medicine (TCM) formula, EXD, was also demonstrated. At last, a novel approach for identification of bioactive components from Chinese medicine formula was introduced using EXD as study model. To evaluate the multiple pharmacological properties of EXD, proteins involved in steroidogenesis in ovaries of aged female rats were measured by immunoblotting analysis. On top of that, serum lipid profiles and the related proteins were determined by colorimetric assay and immunoblotting analysis respectively. Also, anti-osteoporotic properties and drug compatibility of EXD were evaluated by in vitro methods such as proliferation assay, osteoclast differentiation assay, ELISA assay or immunoblotting analysis. Lastly, a novel approach for identification of bioactive components in relation to the subsequent bioactivity from traditional Chinese medicinal formula was introduced using HPLC profiles. From the results, it was demonstrated that EXD can modulate steroidogenesis in aged female rat model at least through up-regulation of ovarian aromatase, protein kinase B and estrogen receptor beta at protein level. Besides, EXD also exerts antihyperlipidemic effects in aged female rats as reflected from the decreased serum total cholesterol and LDL-cholesterol levels via regulation of HMG CoA reductase and LDL-receptor, the key proteins for cholesterol synthesis and LDL-cholesterol clearance. In vitro study has also demonstrated the anti-osteoporotic properties of EXD through stimulation of osteoblast proliferation and inhibition of proliferation and differentiation of osteoclast precursor cells. The later was proved to be mediated by down-regulation of NFATc1 proteins, a key protein for osteoclastogenesis. The roles of the drugs categories according to the drug compatibility of traditional Chinese medicine contributing to the optimal anti-osteoporotic properties of EXD were also elucidated. Since the diverse pharmacological properties of a Chinese medicinal formula are often the results of the effects of complex bioactive constituents in the extract, yet identification of the bioactive components has been a tedious task. Thus in the last part of the study, a novel approach for identification of bioactive component from Chinese medicinal formula has been developed. By comparing the HPLC profiles of EXD extracted by different decoction method in relation to their pharmacological properties, six bioactive chemicals were successfully identified which may contribute to the stimulatory effect of EXD on ovarian aromatase and hepatic catalase expression. / published_or_final_version / Chinese Medicine / Master / Master of Philosophy

abstract / Chinese Medicine / Doctoral / Doctor of Philosophy

L’iatrogénie médicamenteuse à l’hôpital est un problème majeur de santé publique dont les causes sont multiples. La diffusion de recommandations de bonnes pratiques de prescription pourrait permettre de diminuer ce phénomène. L’objectif de cette thèse est de modéliser un vecteur possible des bonnes pratiques de prescription, celui des interventions pharmaceutiques. Ce travail se décline en trois séquences : 1.contexte et justification, 2.développement d’un outil de documentation et d’analyse des interventions pharmaceutiques, 3.évaluation d’un modèle de diffusion des recommandations associant l’intervention d’un pharmacien clinicien intégré dans l’unité de soins à un rappel informatique de l'intervention au moment de la prescription. L’ensemble de ces données assoit la pertinence d’une diffusion des interventions pharmaceutiques basée sur les outils technologiques et les activités de pharmacie clinique. / Medication errors in hospitals have become a major public health problem with multiple causes. The diffusion of prescription guidelines could reduce this phenomenon. The objective of this thesis is to modelize a potential vector of prescription guidelines: the pharmacists’ interventions. This work is declined in three sequences: 1.context and justification, 2.development of a tool for the documentation and the analyse of pharmacists’ interventions, 3.assessment of a model of prescription guidelines diffusion combining intervention of a clinical pharmacist integrated into clinical ward with a computerized reminder of the intervention. Our data supports the relevance of pharmacists’ interventions diffusion based on technological tools and clinical pharmacy activities.

published_or_final_version / Orthopaedic Surgery / Master / Master of Philosophy

published_or_final_version / Computer Science and Information Systems / Master / Master of Philosophy

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.